Journal article
Sphingosine kinase 1 isoform-specific interactions in breast cancer
Molecular Endocrinology, Vol.28(11), pp.1899-1915
2014
PMCID: PMC5414788
PMID: 25216046
Abstract
Sphingosine kinase 1 (SK1) is a signaling enzyme that catalyzes the formation of sphingosine-1-phosphate. Overexpression of SK1 is causally associated with breast cancer progression and resistance to therapy. SK1 inhibitors are currently being investigated as promising breast cancer therapies. Two major transcriptional isoforms, SK143 kDa and SK151 kDa, have been identified; however, the 51 kDa variant is predominant in breast cancer cells. No studies have investigated the protein-protein interactions of the 51 kDa isoform and whether the two SK1 isoforms differ significantly in their interactions. Seeking an understanding of the regulation and role of SK1, we used a triple-labeling stable isotope labeling by amino acids in cell culture-based approach to identify SK1-interacting proteins common and unique to both isoforms. Of approximately 850 quantified proteins in SK1 immunoprecipitates, a high-confidence list of 30 protein interactions with each SK1 isoform was generated via a meta-analysis of multiple experimental replicates. Many of the novel identified SK1 interaction partners such as supervillin, drebrin, and the myristoylated alanine-rich C-kinase substrate-related protein supported and highlighted previously implicated roles of SK1 in breast cancer cell migration, adhesion, and cytoskeletal remodeling. Of these interactions, several were found to be exclusive to the 43 kDa isoform of SK1, including the protein phosphatase 2A, a previously identified SK1-interacting protein. Other proteins such as allograft inflammatory factor 1-like protein, the latent-transforming growth factor β-binding protein, and dipeptidyl peptidase 2 were found to associate exclusively with the 51 kDa isoform of SK1. In this report, we have identified common and isoform-specific SK1-interacting partners that provide insight into the molecular mechanisms that drive SK1-mediated oncogenicity.
Details
- Title
- Sphingosine kinase 1 isoform-specific interactions in breast cancer
- Authors
- Daniel Yagoub (Author) - University of Technology SydneyMarc R Wilkins (Author) - UNSW AustraliaAngelina J Lay (Author) - Centenary InstituteDominik C Kaczorowski (Author) - Centenary InstituteDiana Hatoum (Author) - University of Technology SydneySarah Bajan (Author) - University of Technology SydneyGyorgy Hutvagner (Author) - University of Technology SydneyJack H Lai (Author) - Tufts UniversityWengen Wu (Author) - Tufts UniversityRosetta Martiniello-Wilks (Author) - University of Technology SydneyPu Xia (Author) - Centenary InstituteEileen M McGowan (Author) - Centenary Institute
- Publication details
- Molecular Endocrinology, Vol.28(11), pp.1899-1915
- Publisher
- The Endocrine Society
- DOI
- 10.1210/me.2013-1423
- ISSN
- 1944-9917
- PMID
- 25216046; PMC5414788
- Organisation Unit
- School of Health and Behavioural Sciences - Legacy; School of Health and Sport Sciences - Legacy; University of the Sunshine Coast, Queensland; School of Health - Biomedicine
- Language
- English
- Record Identifier
- 99472506102621
- Output Type
- Journal article
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- Domestic collaboration
- International collaboration
- Web Of Science research areas
- Endocrinology & Metabolism
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